Cai Jing, Wu Xianmin, Li Xiaofei, Ma Chong, Xu Lei, Guo Xiangrui, Li Jianfeng, Wang Haibo, Han Yuechen
Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital Affiliated to Shandong University, Jinan, China.
Key Laboratory of Otorhinolaryngology, National Health Commission (Shandong University), Jinan, China.
ORL J Otorhinolaryngol Relat Spec. 2019;81(4):202-214. doi: 10.1159/000500557. Epub 2019 Jul 24.
Cisplatin is an anti-cancer drug that causes oxotoxic side effects such as impairment of inner ear function and hearing loss. We aimed to investigate the effects of allicin against cisplatin-induced stria vascularis damage in mice, and to clarify the mechanism underlying the protective effects of allicin against ototoxicity. Stria vascularis injury was induced in mice by intraperitoneal injection of cisplatin, which was significantly prevented by pretreatment with allicin. Allicin not only reduced cisplatin-activated expression of cleaved caspase-3 in marginal cells, PVM/Ms (perivascular resident macrophage-like melanocytes), and basal cells of the stria vascularis, but also decreased the expression of poly(ADP-ribose) polymerase-1 (PARP-1) and apoptosis-inducing factor (AIF) nuclear translocation in the stria vascularis cells. Our results demonstrate that allicin plays an effective role in protecting stria vascularis injury induced by cisplatin by inhibiting caspase-dependent, as well as caspase-independent PARP-1-AIF-mediated apoptotic pathways. Therefore, allicin may be useful in preventing cisplatin-induced ototoxicity.
顺铂是一种抗癌药物,会引发耳毒性副作用,如内耳功能受损和听力丧失。我们旨在研究大蒜素对顺铂诱导的小鼠血管纹损伤的影响,并阐明大蒜素对耳毒性保护作用的潜在机制。通过腹腔注射顺铂诱导小鼠血管纹损伤,而大蒜素预处理可显著预防这种损伤。大蒜素不仅降低了顺铂激活的血管纹边缘细胞、血管周围驻留巨噬细胞样黑素细胞(PVM/Ms)和基底细胞中裂解的半胱天冬酶-3的表达,还减少了血管纹细胞中聚(ADP-核糖)聚合酶-1(PARP-1)的表达以及凋亡诱导因子(AIF)的核转位。我们的结果表明,大蒜素通过抑制半胱天冬酶依赖性以及半胱天冬酶非依赖性的PARP-1-AIF介导的凋亡途径,在保护顺铂诱导的血管纹损伤中发挥有效作用。因此,大蒜素可能有助于预防顺铂诱导的耳毒性。